1,721,075 research outputs found
Infection in acute exacerbations of chronic bronchitis: a clinical perspective
No full textAbstractAcute exacerbations of chronic bronchitis (AECB) is an important cause of death and morbidity in developed countries and also has significant economic impact. The disease is characterized by increased dyspnoea, sputum volume and sputum purulence; the most commonly associated pathogens are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. H. influenzae and S. pneumoniae express virulence determinants that directly and indirectly impair mucociliary clearance and incite other consequences that are permissive to microbial persistence.Regarding the use of antibiotics, there is currently a lack of large-scale clinical trials that are sufficiently powerful to provide good evidence-based information. Nonetheless, antimicrobial chemotherapy has repeatedly been shown to confer benefit in patients with moderately severe features of AECB. Simple clinical criteria can be used to identify patients in whom there is a higher likelihood of treatment failure or mortality during AECB. These include significant cardiopulmonary co-morbidity, frequent exacerbations, advanced decline in lung function, malnutrition or other generalized debility, advanced age (> 70 years) and concurrent treatment with corticosteroids. In such patients, an aggressive antimicrobial approach to AECB may be warranted in order to prevent clinical failure or representation. From a clinical perspective, appropriate drugs include those that are stable to β-lactamases, are bactericidal against causative pathogens, penetrate diseased lung tissue in high concentrations and have a good safety profile
Evidence-based medicine: empiric antibiotic therapy in community-acquired pneumonia
No full textA number of national society guidelines exist for empiric management of community-acquired pneumonia but these are, to a large extent, not evidence-based, but based on clinical experience, in vitro data, pragmatism and common sense. Many randomized controlled trials of antibiotic therapy in community-acquired pneumonia have been conducted, but most of these have been powered to demonstrate equivalent efficacy of new treatments in comparison with conventional antimicrobial therapy. Development of new antibiotics has been driven by the emergence of penicillin-resistant Streptococcus pneumoniae, but so far there is no hard evidence that beta-lactam therapy fails in community-acquired pneumonia, at least with the higher doses of penicillins that are commonly used in hospital practice. Nonetheless, newer antibiotics have been deployed including macrolides and quinolones, and have demonstrated equivalent (and in some cases, marginally improved) efficacy to older antibiotic treatments in randomized control trials. A number of studies have shown that it is possible to stratify patients according to severity of illness, to in-patient or out-patient management protocols. These have been validated and refined.</p
Neisseria meningitidis; clones, carriage, and disease
No full textAbstractNeisseria meningitidis, the cause of meningococcal disease, has been the subject of sophisticated molecular epidemiological investigation as a consequence of the significant public health threat posed by this organism. The use of multilocus sequence typing and whole genome sequencing classifies the organism into clonal complexes. Extensive phenotypic, genotypic and epidemiological information is available on the PubMLST website. The human nasopharynx is the sole ecological niche of this species, and carrier isolates show extensive genetic diversity as compared with hyperinvasive lineages. Horizontal gene exchange and recombinant events within the meningococcal genome during residence in the human nasopharynx result in antigenic diversity even within clonal complexes, so that individual clones may express, for example, more than one capsular polysaccharide (serogroup). Successful clones are capable of wide global dissemination, and may be associated with explosive epidemics of invasive disease
Experimental therapies for sepsis directed against tumour necrosis factor
No full textTumour necrosis factor (TNF) has been identified as an important mediator involved in the generation of sepsis syndrome. Two major strategies have evolved for counteracting the effects of TNF in patients with severe manifestations of sepsis: neutralization by anti-TNF antibodies and competitive antagonism of TNF with synthetic soluble TNF receptors. Clinical trials with murine monoclonal antibodies against TNF have shown that this agent is able to reduce early morbidity and mortality, but with no reduction in 28 day mortality. A clinical study with a synthetic 75 kDa soluble TNF receptor failed to show any benefit with this drug and indeed there was higher mortality at higher doses. Trials of a 55 kDa soluble TNF receptor are continuing and this drug is apparently safe. Drugs that modify TNF in vivo may be a useful component of future management of sepsis, either as monotherapy or as part of a combined strategy of immunomodulation.</p
Experimental nasopharyngeal colonization by Neisseria meningitidis using explant organ culture
No full textThis chapter will describe the use of organ cultures of human nasopharyngeal mucosa to study the interaction of Neisseria meningitidis with this complex tissue. Colonization of nasopharyngeal mucosa is the first step in the pathogenesis of meningococcal disease. Supporting evidence for this is the correlation between the prevalence of community carriage and the occurrence of meningococcal disease (1). During nonepidemic periods, the baseline prevalence of nasopharyngeal carriage of meningococci is 5-10% but is considerably higher in certain populations such as military personnel (2), and in households of cases (3). There are a number of influences on the acquisition of meningococcal carriage; these include smoking (4) but not season (5). It is possible that coincident viral infections may affect acquisition of meningococ cal carriage (6,7). There is good evidence that genetic factors are involved, as some individuals appear resistant to acquisition of carriage, while others chronically or intermittently carry N. meningitidis (8). Carriage of the organism also appears to be associated with secretor status (9). The precise site within the nasopharynx that Neisseria meningitidis colonizes and invades is not known. However, during natural carriage, the organism can be isolated both from the rhinopharynx and from the throat (10).</p
- …
